Detection of ALK, RET, ROS1, NTRK1 and MET rearrangements and actionable mutations using next generation sequencing in patients with non-small cell lung cancer

Abstract

and albumin/globular protein (OR 2.02, 95%CI 1.33-3.06) were significantly correlated with KRAS mutation status. A nomogram was established and showed considerable discriminating accuracy (AUC 0.744, 95%CI 0.709-0.779) in this cohort. Patients with the highest score had 88.6% chance to bear a KRAS-mutant tumor. Subgroup analysis based on metastasis status revealed a sound applicability of the established nomogram both in metastatic (AUC 0.723, 95%CI 0.666-0.781) and non-metastatic (AUC 0.753, 95%CI 0.707-0.798) CRC. Conclusions: Six simple and easy-to-collect characteristics defined a useful nomogram to predict KRAS status both in metastatic and non-metastatic CRC with great predic-tive accuracy. Legal entity responsible for the study: Guoxiang Cai. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest. 34P Epigenomics paves a new way to assess potential toxicity and chemotherapeutic response of breast tumours to 5-fluorouracil Background: 5-fluorouracil (5-FU) is widely used in the therapy of solid tumors, including breast cancer (BC). Toxicity remains a major limitation in the clinical efficacy of 5-FU. Developed approximately 50 years ago, this competitive antagonist of uracil is still not exhaustively studied in terms of its mechanism of action, and the potential of molecular markers in predicting its efficacy and toxicity is not yet fully unravelled. Methods: A modified Reduced Representation Bisulfite Sequencing genome-wide DNA methylation analysis assay, XmaI-RRBS, was applied to 170 BC samples obtained before chemotherapy, and to 10 normal breast tissue samples. Unsupervised hierarchical cluster analysis was used to discern intrinsic DNA methylation BC subtypes; clustering uncertainty was assessed with pvclust R package using bootstrap permutation approach. Results: In a DNA methylation BC subtype enriched in triple-negative breast cancer samples we have identified statistically significant enrichment with the samples non-methylated at the promoter region of the NME1 gene, compared to all other DNA methylation BC subtypes. Another finding was abnormal methylation of the DPYS gene in a DNA methylation BC subtype enriched in HER2 positive tumors. Conclusions: Most studies of 5-FU resistance have focused on germline status of thy-midylate synthase TYMS and DPYD genes, and 5-FU Toxicity and Chemotherapeutic Response Panels for the detection of germline variants in these genes are now widely available. It has also been shown that increased expression in tumor cells of some enzymes from the 5-FU metabolic pathway such as DPYD is correlated with resistance to 5-FU. Here we demonstrate differential methylation of the 5-FU drug pathway mediator genes DPYS and NME1 between the DNA methylation BC subtypes. DNA methyl-ation is easily detected by methylation sensitive PCR and does not require RNA extraction. Thus, we suggest that the existing germline DNA tests may be supplemented with the tumour biopsy DNA methylation analysis in order to provide better prediction of 5-FU response and toxicity. Background: Targeted therapies have been developed this last decade and considerably improved PFS and OS of patients with NSCLC. Next-Generation Sequencing (NGS) is commonly used for the detection of actionable mutations in a panel of genes and FISH or IHC are the gold-standard assay for the detection of rearrangements of ALK, RET, ROS1, NTRK1 and MET. The aim of this study is to evaluate the suitability and